Approximately 100,000 adolescents and young adults in the
United States experience a first episode of psychosis (FEP) every year. The
early phase of psychotic illness is widely viewed as a critical opportunity
for indicated prevention, and a chance to alter the downward trajectory and
poor outcomes associated with schizophrenia and related psychotic disorders.
Unfortunately, numerous studies find a substantial delay between the onset of
psychotic symptoms and the initiation of FEP care; in the U.S. treatment is
typically delayed between one and three years. Early identification of FEP,
rapid referral to evidence-based Coordinated Specialty Care (CSC) for early
psychosis, and effective engagement in CSC services are essential to
shortening the duration of untreated psychosis (DUP) and pre-empting the
functional deterioration common in psychotic disorders. The World Health
Organization advocates reducing DUP to 3 months or less. Accordingly, this
Funding Opportunity Announcement (FOA) seeks research project grant
applications that test practical, reproducible strategies for substantially
reducing DUP among persons with FEP in the U.S. by eliminating bottlenecks or
closing gaps in the pathway to CSC services. Alternatively, applicants whose
work in this area is at a developmental stage should consider applying to the
companion R34 FOA PAR-19-235.

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and
Department of Health and Human Services partners. You must use one of these submission
options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online.

Approximately 100,000 adolescents and young adults in the
United States experience a first episode of psychosis (FEP) every year. The
early phase of psychotic illness is widely viewed as a critical opportunity for
indicated prevention and a chance to alter the downward trajectory and poor
outcomes associated with schizophrenia and related psychotic disorders.
Compared to traditional treatment approaches, programs that integrate FEP medication
management, cognitive behavioral therapy, supported employment and education,
family psychoeducation, case management and primary care coordination within a
shared decision making framework, i.e., team-based Coordinated Specialty care
(CSC), have been found to produce a range of positive clinical and functional
outcomes, including reduced symptoms, lower rates of re-hospitalization,
shorter hospital stays, greater involvement in work or school, improved quality
of life and social functioning, increased cognitive performance and decreased
substance abuse. However, the timing of this treatment is critical; short and
long-term outcomes are better when individuals begin treatment close to the
onset of psychosis.

International consensus statements from the World Health
Organization recommend that specialty care for FEP start within 3 months of
illness onset. However, more than two dozen studies conducted worldwide have
observed a substantial delay (on average 2 years) between the appearance of
psychotic symptoms and the initiation of treatment. Multiple meta-analyses
clearly establish that the duration of untreated psychosis (DUP)—the time
between the onset of psychosis and initiation of treatment to address the
psychotic symptoms—is correlated with poor outcomes. In the U.S., DUP ranges
between one and three years, suggesting that many people with FEP are missing a
critical opportunity to benefit from early psychosis intervention.

Research indicates that DUP can be reduced by enhancing
early detection, treatment referral, and CSC engagement mechanisms. Early
identification of FEP, rapid referral to evidence-based CSC, and effective
engagement in CSC services are essential to shortening DUP and pre-empting the
functional deterioration common in psychotic disorders. Reducing DUP in the
U.S. from current levels of 1-3 years to the recommended standard of no more
than 3 months should be a major focus of applied research efforts. Research to
improve FEP case identification and referral to and engagement in CSC in the U.S.
is a logical complement to other NIMH initiatives on improving outcomes for
people with FEP, such as the Recovery After an Initial Schizophrenia Episode (RAISE) initiative, which
found that CSC produced superior clinical and functional improvements compared
to typical care, especially among clients with shorter DUP, and the Early Psychosis Intervention
Network (EPINET), a national early psychosis learning health care endeavor
in the U.S.

CSC services have expanded dramatically in the U.S.,
following the RAISE initiative and additional federal funding to states for
evidence-based FEP treatment programs. Nearly every state now has a CSC
program, with more than 265 CSC programs nationwide serving approximately
10,000 individuals with FEP annually. Systematic efforts to reduce DUP could
help young people with FEP access CSC services at the earliest possible
opportunity and derive the maximum benefit from this evidence-based care.

Accordingly, this Funding Opportunity Announcement (FOA)
seeks research project grant applications that test practical, reproducible
strategies for substantially reducing DUP among persons with FEP in the U.S. by
eliminating bottlenecks or closing gaps in the pathway to CSC
services.

Research Objectives

This FOA aims to support research that will test feasible
and reproducible strategies for substantially reducing DUP among persons with
FEP in real-world U.S. settings. The research should focus on eliminating
bottlenecks or closing gaps in the pathway to specialty FEP care. For this
announcement, we define "bottlenecks" and “gaps” as individual,
organizational, systemic, or other impediments to rapid FEP identification,
assessment, connection to and engagement in specialty FEP care. The target
population is not limited to first episode schizophrenia, but includes all
persons experiencing a first episode of psychosis regardless of presenting
diagnosis. Applicants are encouraged to base research activities in settings
that link to treatment systems with CSC programs for FEP. A variety of
configurations for FEP specialty care programs are possible, but evidence-based
CSC treatment involves integrated, team-based care and typically features use
of single antipsychotic medications, prescribed in low doses; family
psychoeducation; supported employment and education; cognitive-behavioral
therapy oriented to recovery; coordination with primary care services; and
continuity of care across inpatient and outpatient treatment settings.

Applications submitted to this FOA should propose projects
that test practical approaches for producing one or more of the following:

Methods to achieve expeditious referral of persons with FEP, or
those with CHR, to an appropriate specialty care treatment program; and

Strategies for achieving rapid initiation of and engagement in
FEP treatment.

The strategies proposed to reduce DUP should aim to close
gaps as well as remove significant bottlenecks in the referral pathway to CSC,
including barriers that impede the following:

Recognition of psychotic symptoms

Referral to screening for a psychotic disorder with validated
assessment instruments

Diagnosis of a psychotic disorder

Referral to a CSC program

Enrollment in a CSC program and/or initiation of CSC treatment

Engagement in CSC services

Applications submitted to this FOA should consider “supply
side” approaches (e.g., targeting clinical, community, institutional or other
systems), such as the development and testing of strategies for training
primary care physicians and nurses, school and college counselors, emergency
department staff, police, corrections officers and mental health “generalists”
to recognize signs of early psychosis, and the improvement of referral networks
to fast-track the initiation of FEP care. This FOA is also intended to
encourage “demand side” approaches (e.g., engaging people with FEP and their
family members, friends, caregivers and others close to the affected
individual) to improve recognition of early symptoms, help-seeking, access, and
engagement in care for persons with FEP and/or youth with CHR, through education,
decision-support systems, public awareness campaigns, and other tools,
including social marketing, social media and social networking.

Research to reduce DUP requires expertise on the
characteristics of service delivery systems, community settings, or other
settings in which DUP reduction strategies would be embedded, as well as
expertise on the needs, life circumstances, and diversity of the population of
young people with FEP and/or CHR. Investigators should convey knowledge of DUP
assessment strategies and factors that may contribute to treatment delays in
the U.S. health care system. Multi-disciplinary research teams with
complementary areas of expertise are encouraged, as are collaborations with
stakeholders from the target clinical, community or institutional setting. NIMH
strongly encourages the involvement of individuals with FEP and/or CHR and
their family members and friends, in all aspects of developing and testing DUP
reduction interventions, as relevant to the proposed strategy.

In addition, NIMH welcomes applications proposing to
leverage existing practice-based research infrastructures, such as the NIMH-sponsored
Mental Health Research Network (MHRN), the NCATS Trial Innovations
Network, the anticipated EPINET regional scientific hubs, the ThriveNYC
Investigators' Hub, and other practice networks looking to conduct studies
to reduce DUP. NIMH also encourages coordination of DUP reduction research with
other public and private initiatives that specifically address early identification
and treatment of young people at high risk for mental illness. For example,
since 2014 the Substance Abuse and Mental Health Services Administration
(SAMHSA) has supported the implementation of hundreds of evidence-based
treatment programs for FEP across the U.S. via a set-aside in the Community
Mental Health Block Grant Program (CMHBG). These FEP treatment programs
represent a tremendous opportunity for advancing DUP reduction
research. Likewise, in 2018, through its Clinical
High Risk for Psychosis (CHR-P) initiative, SAMHSA
funded 21 service delivery
programs to identify individuals with CHR-P and provide treatment to
prevent the onset of psychosis and/or improve symptoms and functioning. These
CHR-P treatment programs represent another promising setting for DUP reduction
research.

This FOA, and the related FOA, PAR-19-235,
support experimental and quasi-experimental studies focused on designing,
refining, and testing systematic, practical and accurate case identification of
persons with FEP and/or CHR within a myriad of possible clinical, community and
institutional contexts, in combination with strategies that promote rapid
referral to and engagement in the appropriate stage-specific specialty
care.

Research
Topics

Applications to this FOA should focus on practical and
reproducible strategies to achieve substantial DUP reduction for persons with
FEP. NIMH strongly encourages applications in which referral to evidence-based
CSC programs is feasible. This FOA supports studies on the research topics
listed below, which are intended to be illustrative, not exhaustive:

Improving recognition of symptoms and increasing help-seeking
behavior among people with FEP and CHR.

Improving recognition of symptoms and increasing help-seeking
behavior among people with FEP, who often experience the highest levels of
health disparities, including members of racial or ethnic minority groups or
persons who identify as lesbian, gay, bisexual or transgender.

Improving recognition of early psychosis symptoms among family
members and friends of persons with FEP and facilitating their help-seeking and
supportive behaviors on behalf of individuals with FEP.

Improving case identification and referral of patients with FEP
within non-specialty clinical, community and institutional systems (e.g.,
pediatrics, primary care, high schools, criminal justice settings, college
campuses, or workplace), as well as within child/youth and adult specialty
mental health settings.

Developing and testing decision support tools, including those
embedded in electronic health records, for improving the early identification
of FEP and CHR and matching of symptomatic and functional deficits with
available service systems within a catchment area.

Testing the effectiveness of strategies within emergency
departments and inpatient facilities to improve identification and referral of
patients with FEP to appropriate stage-specific FEP care and promote care
engagement.

Partnering with police departments, including those with Crisis
Intervention Teams, to recognize possible symptoms of psychosis and divert
eligible individuals to appropriate FEP screening and/or care, as indicated.

Assessing the impact of CHR/FEP public awareness campaigns on
initiation of treatment and shortening DUP.

Social marketing, social media, and social networking approaches
to identify persons with CHR or FEP and link them to treatment.

Improving access to and engagement in care for persons with CHR,
resulting in rapid FEP identification and entry into specialty CSC care for
individual who convert to psychosis.

It is expected that applications submitted to this FOA will
identify other important, innovative and impactful research
topics. Investigators considering applying to this FOA are strongly encouraged
to contact the Scientific/Research
Contact for this FOA before submitting an application.

A variety of rigorous methodological approaches are possible
for testing the impact of the proposed approach to reducing DUP. These
approaches include randomized controlled trials, stepped-wedge trials,
interrupted time series designs, quasi-experimental designs with non-randomized
comparison groups, and other designs of equivalent rigor and relevance.
Considerations for selecting a research design for the proposed study include
the scientific question that the study is designed to answer, practical
constraints, ethical issues, and the tradeoff between maximizing internal and
external validity.

Investigators in this area whose work is at a developmental
stage should consider applying to the companion FOA, PAR-19-235.

Note that this FOA requires a clinical trial. DUP reduction
projects that don’t involve a clinical trial are encouraged through other
funding mechanisms, including the following (and any future re-issuances of the
same):

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible
to apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM)–
Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number to register in eRA Commons. Organizations can
register with the eRA Commons as they are working through their SAM or
Grants.gov registration, but all registrations must be in place by time of
submission. eRA Commons requires organizations to identify at least one Signing
Official (SO) and at least one Program Director/Principal Investigator (PD/PI)
account in order to submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another
application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an
Application Package

The application forms package specific to this opportunity
must be accessed through ASSIST, Grants.gov Workspace or an institutional
system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are
available in Part 1 of this
FOA. See your administrative office for instructions if you plan to use an
institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

Facilities
and Other Resources: The description of the resources and
environment should address how the study utilizes existing infrastructure
(e.g., practice-based research networks, electronic medical records,
administrative data bases, patient registries) or other available resources to
increase the efficiency of participant recruitment and data collection,
explicitly address how efficiencies are incorporated or provide a justification
in the event that such efficiencies cannot be incorporated.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

Biographical
Sketch

Document investigators' knowledge of DUP assessment strategies
and factors that may contribute to treatment delays in the U.S. health care
system. The biographical sketches should also document the qualifications of
the PD/PI and other senior investigators, including expertise in the
identification and treatment of people with FEP and expertise in the service
delivery systems or institutional or community settings in which the selected
DUP reduction strategies would be embedded, and expertise in conducting
research in real-world community treatment settings.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Justify the practical effect of the intervention or service
approach in terms of the estimated hypothesized effect size (in terms of key
outcomes, such as clinical benefit, safety/tolerability, value and efficiency,
or scalability), compared with already available approaches. Address the
potential impact of the intervention/service delivery approach in terms of both
(1) the empirical basis for the anticipated effect size (e.g., citing data
regarding the magnitude of the association between the target and the clinical
endpoint of interest and/or effect sizes obtained in prior efficacy studies),
and (2) the clinical meaningfulness of the anticipated increment in effects
compared to existing approaches.

Applications are expected to maximize efficiencies in
effectiveness research (e.g., by utilizing existing infrastructure such as
practice-based research networks, electronic medical records, administrative
data bases, patient registries, or other available resources) and should
explicitly address how efficiencies are incorporated.

Address the degree to which the proposed intervention/service delivery
approach is scalable and could be disseminated into practice, given typically
available resources (e.g., trained, skilled providers), typical service
structures (including MH financing), and typical service use patterns.

Explain how the scientific rationale and need for a clinical
trial to test the proposed DUP reduction hypothesis or intervention are well
supported by preliminary data, clinical and/or preclinical studies, or
information in the literature or knowledge of biological mechanisms. For trials
focusing on clinical or public health endpoints, indicate (1) why this clinical
trial is necessary for testing the safety, efficacy or effectiveness of the
proposed DUP reduction intervention, and (2) how the intervention could lead to
a change in clinical practice, community behaviors or health care policy. For
trials focusing on mechanistic, behavioral, physiological, biochemical, or
other biomedical endpoints, justify why this trial is needed to advance
scientific understanding.

Innovation

Highlight novel strategies proposed for reducing DUP among people
with FEP, as applicable.

Highlight any innovative approaches for assessing DUP in institutional
or community treatment settings via measures that are valid, reliable, and
practical.

Highlight how innovative research strategies and design/analytic
elements (e.g., adaptive sequential randomization, equipoise stratification)
are incorporated, as appropriate, in order to enhance the study's sensitivity
or potential to advance scientific knowledge or clinical practice.

Approach

Applications should present empirical data that support the
feasibility and acceptability of the proposed strategy for reducing DUP. The
empirical data presented for the selected setting should (1) quantify the
overall DUP among persons with FEP at baseline using a scientifically
acceptable operational definition of DUP and reliable measures of DUP, (2) map
the various referral pathways that channel persons with FEP to FEP specialty
care programs, and (3) identify gaps and bottlenecks in these referral pathways
that prolong DUP.

Applications should propose a DUP reduction approach that has the
potential to substantially reduce DUP in the target population of people with
FEP by eliminating bottlenecks or closing gaps in the pathway to CSC services.
The application should describe how reduction in DUP will be included as the
primary outcome.

The application should provide justification that the DUP
reduction intervention, if demonstrated effective, could be implemented and
sustained in typical community or service settings using typically available
personnel and resources.

Detail the plan to explicitly address whether the intervention to
reduce DUP engages the mechanism that is presumed to underlie intervention
effects (i.e., the mechanism that accounts for changes in DUP). Include
the following: (1) a conceptual framework that clearly identifies the
target(s)/mechanism(s) and the empirical evidence linking the
target(s)/mechanism(s) to DUP reduction; (2) plans for assessing engagement of
the target(s)/mechanism(s) using valid measures that are as direct and
objective as is feasible in the effectiveness context, including the specific
measures, the assessment schedule, and the justification for the assessment
strategy (e.g., evidence regarding the validity and feasibility of the proposed
measures in the effectiveness context); and (3) a
statistical analysis plan and corresponding power calculations for data
analyses that will be used to examine whether the intervention engages the
target(s) and whether intervention-induced changes in the target(s) are
associated with DUP reduction (i.e., mediation). In the case of
multi-component interventions, the application should specify the conceptual
basis, assessment plan, and analytic strategy, as detailed above, for the
target(s)/mechanism(s) corresponding to each DUP reduction intervention
component, as appropriate in the effectiveness context.

When appropriate, for studies that involve preventive or
therapeutic interventions, detail how the study takes into account RDoC or
RDoC-like constructs when defining the subject eligibility (inclusion),
intervention targets or mechanisms, and outcomes, as feasible in the
effectiveness setting.

Describe provisions for the assessment and monitoring of the fidelity
of intervention delivery via procedures that are feasible and valid for use in
community practice settings.

Describe plans to collaborate on the research process—including
project design—with community practice partners/providers, mental health service
users and their family members, relevant policy makers, and other relevant
stakeholders in a manner that informs the research and helps to ensure the
results will have utility.

When appropriate, incorporate secondary outcome measures that are
validated and generally accepted by the field, including stakeholder-relevant
outcomes (e.g., functioning or health services use).

When appropriate, describe plans to collect data on potential
moderators such as clinical and biological variables (e.g., blood for genetic
analysis, other potential biomarkers) that might be used to inform or test
algorithms for more prescriptive approaches in future work.

Indicate how the trial design and research protocol are consistent
with CONSORT guidelines, as appropriate.

As relevant, address how the trial contributes to advancing the
personalization of mental health care and describe the collection of clinical
and biological variables (e.g., blood for genetic analysis, other potential
biomarkers) that might be used to examine moderators or inform/test algorithms
for more prescriptive approaches. Address statistical power to test for
moderators and/or the potential to contribute information regarding potential
moderators to larger databases for future use.

For studies that involve the assessment of patient-level
outcomes, plans are expected that describe the assessment of suicidal behavior
and related outcomes using strategies that can facilitate integration and
sharing of data (e.g., see NOT-MH-15-009 and
the PhenX Toolkit for constructs
and corresponding assessment strategies), as appropriate, or provide a
rationale for excluding such measures if they are not
included. Accordingly, the application should provide the rationale for
the selection of suicide-related constructs and corresponding assessment instruments
(e.g., measures of ideation, attempts), the time periods assessed (e.g.,
lifetime history, current), and the assessment schedule for administration
(e.g., baseline, during intervention, post-intervention, follow up), taking
into account the nature of the target population, participant burden,
etc. The application should also address provisions for clinical
management when suicidal behavior is reported. In situations where it is not
appropriate or feasible to include assessment of suicide outcomes due to the
nature of the intervention (e.g., services interventions that target provider
behavior or systems-level factors), the target population (e.g., very young
children), or unique issues related to participant burden or safety/monitoring
concerns, the application should provide an appropriate justification for
excluding these assessments.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

In order to facilitate the goal of advancing research
through widespread data sharing among researchers, investigators funded under
this FOA are expected to share those data via the National Database for
Clinical Trials related to Mental Illness (NDCT; http://ndct.nimh.nih.gov/; see NOT-MH-14-015 and NOT-MH-15-012).
Established by the NIH, NDCT is a secure informatics platform for scientific
collaboration and data-sharing that enables the effective communication of
detailed research data, tools, and supporting documentation. NDCT links data
across research projects through its Global Unique Identifier (GUID) and Data
Dictionary technology. Investigators funded under this FOA are expected to use
these technologies to submit data to NDCT.

To accomplish this objective, it will be important to
formulate a) an enrollment strategy that will obtain the information necessary
to generate a GUID for each participant, and b) a budget strategy that will
cover the costs of data submission. The NDCT web site provides two tools to
help investigators develop appropriate strategies: 1) the NDCT Budgeting
Spreadsheet http://ndct.nimh.nih.gov/preplanning/budget -
a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal
Investigator and Data Manager to budget for data sharing; and 2) plain language
text to be considered in your informed consent http://ndct.nimh.nih.gov/preplanning/informed-consent. Investigators are expected to certify the quality of all data generated by
grants funded under this FOA prior to submission to NDCT and review their data
for accuracy after submission. Submission of descriptive/raw data is expected
semi-annually (every January 15 and July 15); submission of all other data is
expected at the time of publication, or prior to the end of the grant,
whichever occurs first (see Data Sharing Expectation http://ndct.nimh.nih.gov/preplanning/#tab-1 for
more information); Investigators are expected to share results, positive and
negative, specific to the cohorts and outcome measures studied by using the
Study functionality(see http://ndct.nimh.nih.gov/results). The
NDCT Data Sharing Plan is available for review on the NDCT web site (http://ndct.nimh.nih.gov/wp-content/uploads/NDCT_Data_Sharing_Policy_20141002.pdf).
NDCT staff will work with investigators to help them submit data types not yet
defined in the NDCT Data Dictionary http://ndct.nimh.nih.gov/submit/data-dictionary.

Appendix:

Only limited Appendix materials are allowed. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical
research, and/or clinical trials (and when applicable, clinical trials research
experience) follow all instructions for the PHS Human Subjects and Clinical
Trials Information form in the SF424 (R&R) Application Guide, with the
following additional instructions:

If you answered “Yes” to the question “Are Human Subjects
Involved?” on the R&R Other Project Information form, you must include at
least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials
Information form or Delayed
Onset Study record.

Study
Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide
must be followed with the following additional instructions:

Applicants must upload the attachments for Intervention
Manual/Materials as separate files, as applicable. Applicants must use the
"Intervention Manual/Materials" to name these other attachments files
and label each attachment with a unique filename, e.g. ‘Intervention Manual.1’
for Study Record 1, ‘Intervention Manual.2’ for Study Record 2, etc. As
appropriate, this may include screenshots of mobile interventions,
technological specifications, training manuals or treatment algorithms.

Delayed
Onset Study

Note: Delayed
onset does NOT apply to a study that can be described but will not start
immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide
must be followed.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), NATO
Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and
Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission. When a
submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date and time. If a Changed/Corrected application is submitted after the
deadline, the application will be considered late. Applications that miss the
due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit How to
Apply – Application Guide. If you encounter a system issue beyond your
control that threatens your ability to complete the submission process on-time,
you must follow the Dealing
with System Issues guidance. For assistance with application
submission, contact the Application Submission Contacts in Section VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization’s profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness and compliance with application instructions by the Center for
Scientific Review, NIH. Applications that are incomplete or non-compliant will
not be reviewed.

Use of Common Data Elements in
NIH-funded Research

NIMH encourages the use of common data elements (CDEs) in
basic, clinical, and applied research, patient registries, and other human
subject research to facilitate broader and more effective use of data and
advance research across studies. CDEs are data elements that have been
identified and defined for use in multiple data sets across different studies.
Use of CDEs can facilitate data sharing and standardization to improve data
quality and enable data integration from multiple studies and sources,
including electronic health records. NIH ICs have identified CDEs for many
clinical domains (e.g., neurological disease), types of studies (e.g.
genome-wide association studies (GWAS)), types of outcomes (e.g.,
patient-reported outcomes), and patient registries (e.g., the Global Rare
Diseases Patient Registry and Data Repository). NIH has established a
"Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in
identifying NIH-supported CDEs when developing protocols, case report forms,
and other instruments for data collection. The Portal provides guidance about
and access to NIH-supported CDE initiatives and other tools and resources for
the appropriate use of CDEs and data standards in NIH-funded
research. Investigators are encouraged to consult the Portal and describe
in their applications any use they will make of NIH-supported CDEs in their
projects.

Applicants requesting $500,000 or more in direct costs in
any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application
and follow the Policy on the Acceptance for Review of Unsolicited Applications
that Request $500,000 or More in Direct Costs as described in the SF424
(R&R) Application Guide.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in the policy.
Any instructions provided here are in addition to the instructions in the
policy.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review
system.

A proposed Clinical Trial
application may include study design, methods, and intervention that are not by
themselves innovative but address important questions or unmet needs.
Additionally, the results of the clinical trial may indicate that further
clinical development of the intervention is unwarranted or lead to new avenues
of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? Is the prior research that serves as
the key support for the proposed project rigorous? If the aims of the project
are achieved, how will scientific knowledge, technical capability, and/or
clinical practice be improved? How will successful completion of the aims
change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field? Does
the proposed approach have the potential to substantially reduce DUP in the
target population of people with FEP?

Does the application justify the practical effect of
the DUP reduction intervention or service approach in terms of the estimated
hypothesized effect size (in terms of key outcomes, such as clinical benefit,
safety/tolerability, value and efficiency, or scalability), compared with
already available approaches? Does the application adequately address both (1)
the empirical basis for the anticipated effect size (e.g., citing data
regarding the magnitude of the association between the target and the clinical
endpoint of interest and/or effect sizes obtained in prior efficacy studies),
and (2) the clinical meaningfulness of the anticipated increment in effects
compared to existing approaches?

If the proposed DUP reduction approach is successful,
is it scalable and could it be disseminated into practice given typically
available resources (e.g., trained, skilled providers), typical service
structures (including health care financing), and typical service use
patterns?

Are the scientific rationale and need for a clinical
trial to test the proposed hypothesis or intervention well supported by
preliminary data, clinical and/or preclinical studies, or information in the
literature or knowledge of biological mechanisms? For trials focusing on clinical
or public health endpoints, is this clinical trial necessary for testing the
safety, efficacy or effectiveness of an intervention that could lead to a
change in clinical practice, community behaviors or health care policy? For
trials focusing on mechanistic, behavioral, physiological, biochemical, or
other biomedical endpoints, is this trial needed to advance scientific
understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or those in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Do the qualifications of the PD/PI
and other senior investigators include expertise in the identification and
treatment of people with FEP and expertise in the service delivery systems or institutional
or community settings in which the selected DUP reduction strategies would be
embedded? Do research team members have complementary areas of
expertise?

With regard to the proposed
leadership for the project, do the PD/PI(s) and key personnel have the
expertise, experience, and ability to organize, manage and implement the
proposed clinical trial and meet milestones and timelines? Do they have
appropriate expertise in study coordination, data management and statistics?
For a multicenter trial, is the organizational structure appropriate and does
the application identify a core of potential center investigators and staffing
for a coordinating center?

Innovation

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Are
novel strategies proposed for reducing DUP among people with FEP and/or measuring
DUP in institutional or community treatment settings in the U.S.?

Does the design/research plan
include innovative elements, as appropriate, that enhance its sensitivity,
potential for information or potential to advance scientific knowledge or clinical
practice?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Have
the investigators included plans to address weaknesses in the rigor of prior
research that serves as the key support for the proposed project? Have the
investigators presented strategies to ensure a robust and unbiased approach, as
appropriate for the work proposed? Are potential problems, alternative
strategies, and benchmarks for success presented? If the project is in the
early stages of development, will the strategy establish feasibility and will
particularly risky aspects be managed? Have the investigators presented
adequate plans to address relevant biological variables, such as sex, for studies
in vertebrate animals or human subjects?

If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects
from research risks, and

2) inclusion (or exclusion) of individuals on the
basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion
of individuals of all ages (including children and older adults), justified in
terms of the scientific goals and research strategy proposed?

Does the application present empirical data that
support the feasibility and acceptability of the proposed strategy for reducing
DUP? Does the project include a scientifically acceptable operational
definition of DUP? Are methods described for obtaining reliable estimates of DUP
in community or institutional programs? Does the project include DUP reduction
for persons with FEP as a primary outcome?

As appropriate, will the plan for involving
collaborations and/or input from community practice partners/providers, mental
health service users, family members, policy makers and other relevant
stakeholders inform the DUP reduction research strategy and the research plan
and help to ensure the results will have utility?

Does the application adequately address the
following, if applicable:

Study
Design

Is the study design justified and appropriate to
address primary and secondary outcome variable(s)/endpoints that will be clear,
informative and relevant to the hypothesis being tested? Is the scientific
rationale/premise of the study based on previously well-designed preclinical
and/or clinical research? Given the methods used to assign participants and
deliver the DUP reduction intervention, is the study design adequately powered
to answer the research question(s), test the proposed hypothesis/hypotheses,
and provide interpretable results? Is the trial appropriately designed to
conduct the research efficiently? Are the study populations (size, gender, age,
demographic group), proposed intervention arms/dose, and duration of the trial,
appropriate and well justified?

Are potential ethical issues adequately addressed? Is
the process for obtaining informed consent or assent appropriate? Is the
eligible population available? Are the plans for recruitment outreach,
enrollment, retention, handling dropouts, missed visits, and losses to
follow-up appropriate to ensure robust data collection? Are the planned
recruitment timelines feasible and is the plan to monitor accrual adequate? Has
the need for randomization (or not), masking (if appropriate), controls, and
inclusion/exclusion criteria been addressed? Are differences addressed, if
applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and
monitor adherence to, the trial protocol and data collection or distribution
guidelines appropriate? Does the application propose to use existing available
resources, as applicable?

Data
Management and Statistical Analysis

Are planned analyses and statistical approach
appropriate for the proposed study design and methods used to assign
participants and deliver interventions? Are the procedures for data management
and quality control of data adequate at clinical site(s) or at center
laboratories, as applicable? Have the methods for standardization of procedures
for data management to assess the effect of the intervention and quality
control been addressed? Is there a plan to complete data analysis within the
proposed period of the award?

How well does the study design address whether the
intervention engages the mechanism that is presumed to underlie the DUP
reduction intervention effects (the mechanism that accounts for changes in DUP)? To
what extent does the application include (1) a well-supported conceptual
framework that clearly identifies the target(s)/mechanism(s) and the empirical
evidence linking the target(s)/mechanism(s) to DUP; (2) well justified plans
for assessing engagement of the target(s)/mechanism(s), including the specific
measures, the assessment schedule, and the justification for the assessment
strategy (e.g., evidence regarding the validity and feasibility of the proposed
measures in the effectiveness context); and (3) an appropriate analytic
strategy and corresponding power calculations for data analyses that will be
used to examine whether the intervention engages the target(s) and whether
intervention-induced changes in the target(s) are associated with reduced DUP (i.e.,
mediation)? Is the study sufficiently powered to examine mediators of
intervention effects? In the case of multi-component DUP reduction
interventions, does the application specify the conceptual basis, assessment
plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s)
corresponding to each intervention component, as appropriate in the
effectiveness context?

When appropriate, for studies that involve preventive
or therapeutic interventions, does the study take into account RDoC or
RDoC-like constructs when defining the subject eligibility (inclusion),
intervention targets or mechanisms, and outcomes, as feasible in the
effectiveness setting?

Does the application include provisions for the
assessment and monitoring of the fidelity of the DUP reduction intervention
delivery via procedures that are feasible and valid for use in the intended settings?

Are the trial design and description of the research
protocol consistent with CONSORT guidelines, as appropriate?

For studies proposing adaptations of existing
interventions for broader use, is the justification for the proposed adaptation
based on data describing characteristics of subgroups of individuals, settings,
care providers or other relevant variables that are associated with partial or
non-response to or poor uptake of DUP reduction strategies?

As relevant, will the trial contribute to advancing
the personalization of mental health care? If relevant, does it include
collection of clinical and biological variables (e.g., blood for genetic
analysis, other potential biomarkers), as appropriate, that might be used to
inform or test algorithms for more prescriptive approaches? Will the study
have either adequate statistical power to test for moderators or the potential
to contribute information to larger databases for future use?

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangements?

If proposed, are the administrative, data
coordinating, enrollment and laboratory/testing centers, appropriate for the
trial proposed?

Does the application adequately address the
capability and ability to conduct the trial at the proposed site(s) or centers?
Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the
application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the
ability of the individual site or center to: (1) enroll the proposed numbers;
(2) adhere to the protocol; (3) collect and transmit data in an accurate and
timely fashion; and, (4) operate within the proposed organizational structure?

As appropriate, are the plans achievable for
establishing necessary agreements with all partners (e.g., single IRB) in a
timely manner?

Does the study utilize existing infrastructure (e.g.,
practice-based research networks, electronic medical records, administrative
data bases, patient registries, or other available resources) or utilize other
available resources to increase the efficiency of participant recruitment and
data collection or provide justification in the event that such efficiencies
cannot be incorporated?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Study Timelines

Is the study timeline described in detail, taking
into account start-up activities, the anticipated rate of enrollment, and
planned follow-up assessment? Is the projected timeline feasible and well
justified? Does the project incorporate efficiencies and utilize existing
resources (e.g., CTSAs, practice-based research networks, electronic medical
records, administrative database, or patient registries) to increase the
efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions
discussed (e.g., strategies that can be implemented in the event of enrollment
shortfalls)?

Protections for Human Subjects

For research that involves human subjects
but does not involve one of the categories of research that are exempt under 45
CFR Part 46, the committee will evaluate the justification for involvement of
human subjects and the proposed protections from research risk relating to
their participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the categories of research
that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the
justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals
Across the Lifespan

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of individuals of all ages (including children and older adults) to
determine if it is justified in terms of the scientific goals and research
strategy proposed. For additional information on review of the Inclusion
section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

Not Applicable

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

For Resubmissions, the committee
will evaluate the application as now presented, taking into consideration the
responses to comments from the previous scientific review group and changes
made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will
consider the appropriateness of the proposed expansion of the scope of the
project. If the Revision application relates to a specific line of
investigation presented in the original application that was not recommended
for approval by the committee, then the committee will consider whether the
responses to comments from the previous scientific review group are adequate
and whether substantial changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider
each of the following items, but will not give scores for these items, and
should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information
provided in this section of the application, including 1) the Select Agent(s)
to be used in the proposed research, 2) the registration status of all entities
where Select Agent(s) will be used, 3) the procedures that will be used to
monitor possession use and transfer of Select Agent(s), and 4) plans for
appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NIMH, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned to the appropriate NIH
Institute or Center. Applications will compete for available funds with all
other recommended applications . Following initial peer review, recommended applications
will receive a second level of review by the National Advisory Mental Health Council.
The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to Part 1 for dates for peer review, advisory council
review, and earliest start date.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any
recent legislation and policy applicable to awards that is highlighted on this
website.

Individual awards are based on the application submitted to,
and as approved by, the NIH and are subject to the IC-specific terms and
conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more
clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the
"responsible party" must register and submit results information for
certain “applicable clinical trials” on the ClinicalTrials.gov Protocol
Registration and Results System Information Website (https://register.clinicaltrials.gov).
NIH expects registration and results reporting of all trials whether required
under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee
Approval: Grantee institutions must ensure that all protocols are reviewed by
their IRB or IEC. To help ensure the safety of participants enrolled in
NIH-funded studies, the awardee must provide NIH copies of documents related to
all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety
monitoring requires oversight and monitoring of all NIH-conducted or -supported
human biomedical and behavioral intervention studies (clinical trials) to
ensure the safety of participants and the validity and integrity of the data.
Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption
Requirements: Consistent with federal regulations, clinical research projects
involving the use of investigational therapeutics, vaccines, or other medical
interventions (including licensed products and devices for a purpose other than
that for which they were licensed) in humans under a research protocol must be
performed under a Food and Drug Administration (FDA) investigational new drug
(IND) or investigational device exemption (IDE).

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color,
national origin, disability, age and, in some circumstances, sex and religion.
This includes ensuring your programs are accessible to persons with limited
English proficiency. HHS recognizes that research projects are often limited
in scope for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

In accordance with the statutory provisions contained in
Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal
Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal
Awardee Performance and Integrity Information System (FAPIIS) requirements.
FAPIIS requires Federal award making officials to review and consider
information about an applicant in the designated integrity and performance
system (currently FAPIIS) prior to making an award. An applicant, at its
option, may review information in the designated integrity and performance
systems accessible through FAPIIS and comment on any information about itself
that a Federal agency previously entered and is currently in FAPIIS. The
Federal awarding agency will consider any comments by the applicant, in
addition to other information in FAPIIS, in making a judgement about the
applicant’s integrity, business ethics, and record of performance under Federal
awards when completing the review of risk posed by applicants as described in
45 CFR Part 75.205 “Federal awarding agency review of risk posed by
applicants.” This provision will apply to all NIH grants and cooperative
agreements except fellowships.

A final RPPR, invention statement,
and the expenditure data portion of the Federal Financial Report are required for
closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

In accordance with the regulatory requirements provided at
45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have
currently active Federal grants, cooperative agreements, and procurement
contracts from all Federal awarding agencies with a cumulative total value
greater than $10,000,000 for any period of time during the period of
performance of a Federal award, must report and maintain the currency of
information reported in the System for Award Management (SAM) about civil,
criminal, and administrative proceedings in connection with the award or
performance of a Federal award that reached final disposition within the most
recent five-year period. The recipient must also make semiannual
disclosures regarding such proceedings. Proceedings information will be
made publicly available in the designated integrity and performance system
(currently FAPIIS). This is a statutory requirement under section 872 of
Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010
of Public Law 111-212, all information posted in the designated integrity and
performance system on or after April 15, 2011, except past performance reviews
required for Federal procurement contracts, will be publicly available. Full
reporting requirements and procedures are found in Appendix XII to 45 CFR Part
75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions
regarding ASSIST, eRA Commons, application errors and warnings, documenting
system problems that threaten submission by the due date, and post-submission
issues)